Two distinct cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI PDE) isoenzyme families, cGIP1 and cGIP2, have been identified. They are products of distinct but related genes. Although activation of cGIP1 is thought to be important in the antilipolytic action of insulin, its role in development is unknown. An approx. 7-kb genomic clone, McGIP1, containing Exon 1 was used to build a replacement vector to target the McGIP1 gene by homologous recombination (knock out). The construct included a negative selection marker (thymidine kinase gene) in 3' end of the genomic fragment and a positive selection marker (neomycin resistance gene, (approx. 1.2 kb)) replacing approx. 600 bp of Exon 1. An intronic probe (from outside the construct) will be used to detect the integrated replacement genomic fragment.